%0 Journal Article
%T The Emerging Role of Innate Immunity in Alzheimer's Disease
%A Deepak Kumar Vijaya Kumar
%A Robert D Moir
%J Archive of "Neuropsychopharmacology".
%D 2017
%R 10.1038/npp.2016.226
%X The amyloid cascade hypothesis is the dominant model for Alzheimer's disease (AD) pathology and has guided AD drug development strategies for over two decades. The hypothesis states that excessive cerebral accumulation of ¦Â-amyloid plaques from oligomerization of amyloid-¦Â protein (A¦Â) drives a neurodegenerative cascade, including generation of neurofibrillary tangles (NFTs) from tau protein. NFTs are a hallmark pathology for AD. Overwhelming genetic and biochemical data support the primacy of A¦Â fibrillization pathways in AD pathology. A landmark study by Choi et al (2014) also recently confirmed that ¦Â-amyloid generation leads to NFTs in novel 3D human neuronal cell culture models that recapitulate AD pathologies (Choi et al, 2014). However, the roles played by A¦Â and ¦Â-amyloid in the amyloid cascade model has shifted markedly during the last two decades. Initially, insoluble ¦Â-amyloid plaques were viewed as driving neurodegeneration. The key species mediating AD pathology are now thought to be soluble oligomeric intermediates generated during A¦Â fibrillization. The near future may see further substantial adjustments to the amyloid cascade model if recent findings of an antimicrobial function for A¦Â, and links between AD and innate immune genes (Bertram and Tanzi, 2012) are confirmed. Importantly, new innate immune models of AD amyloidosis are likely to be of considerable interest for ongoing and future AD therapeutic efforts (Figure 1)
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5143513/